反应详情

温度

87 °C

To a stirred solution of 3—[(R)—1—(2,6—dichloro—3—fluoro—phenyl)—ethoxy]—5 —(4,4,5,5—tetramethyl—[1,3,2]dioxaborolan—2—yl)—pyridin—2—ylamine (4.2711 g, 10.0 mmol) and 4—(4—bromo—pyrazol—1—yl)—piperidine—1—carboxylic acid tert—butyl ester (3.9628 g, 12.0 mmol) in DME (40 mL) was added a solution of Na2CO3 (3.1787 g, 30.0 mmol) in water (10 mL). The solution was degassed and charged with nitrogen three times. To the solution was added Pd(PPh3J2CI2 (351 mg, 0.50 mmol). The reaction solution was degassed and charged with nitrogen again three times. The reaction solution was stirred at 87° C. oil bath for about 16 hours (or until consumption of the borane pinacol ester), cooled to ambient temperature and diluted with EtOAc (200 mL). The reaction mixture was filtered through a pad of celite and washed with EtOAc. The EtOAc solution was washed with brine, dried over Na2SO4, and concentrated. The crude product was purified on a silica gel column eluting with EtOAc/hexane system (0% EtOAc to 100% EtOAc) to afford 4—(4—{6—amino—5—[(R)—1—(2,6—dichloro—3—fluoro—phenyl)—ethoxy]—pyridin—3—yl}—pyrazol—1—yl)—piperidine—1—carboxylic acid tert—butyl ester (3.4167 g, 65% yield, −95% purity) with a Rf of 0.15 (50% EtOAc/Hexanes). MS m/e 550 (M+1)+.

1. customThe solution was degassed
2. additioncharged with nitrogen three times
3. additionTo the solution was added Pd(PPh3J2CI2 (351 mg, 0.50 mmol)
4. customThe reaction solution was degassed
5. additioncharged with nitrogen again three times
6. customuntil consumption of the borane pinacol ester),
7. temperaturecooled to ambient temperature
8. additiondiluted with EtOAc (200 mL)
9. filtrationThe reaction mixture was filtered through a pad of celite
10. washwashed with EtOAc
11. washThe EtOAc solution was washed with brine
12. dry with materialdried over Na2SO4
13. concentrationconcentrated
14. customThe crude product was purified on a silica gel column
15. washeluting with EtOAc/hexane system (0% EtOAc to 100% EtOAc)